USPTO Patents Application 10687850

per

WORLD INTELLECTUAL PROPERTY ORGANIZATION
International Bureau

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)

(51) International Patent Classification 5 :

G01N33/49, 27/26

Al

(11) International Publication Number:
(43) International Publication Date:

WO 93/09433

13 May 1993(13.05.93)

(21) International Application Number: PCT/US92/09678

(22) International Filing Date: 9November 1992(09.11.92)

(30) Priority data:
790,669

8 November 1991 (08.1 1.91) US

(71) Applicant: VIA MEDICAL CORPORATION [US/US];

10633 Roselle Street, San Diego, CA 92I2I (US).

(72) Inventor: GHARIB, James, E. ; 6725 Greenbrier Court,

San Diego, CA 92120 (US).

(74) Agent: BRUEGGEMANN, James, R.; Pretty, Schroeder,
Brueggemann & Clark, 444 South Flower Street, Suite
2000, Los Angeles, CA 90071-2921 (US).

(81) Designated States: DE, GB, JP, European patent (AT, BE,
CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL,
SE).

Published

With international search report.
Before the expiration of the time limit for amending the
claims and to be republished in the event of the receipt of
amendments.

(54)Tffle: ELECTROCHEMICAL MEASUREMENT SYSTEM HAVING INTERFERENCE REDUCTION CIRCUIT

23

JG0///V.-

(57) Abstract

A system for electrically measuring certain chemical characteristics of electrically-conductive fluids, such as blood, located
within a tube and subject to electrical current interference. The measurements are made by measuring the voltage potential be-
tween a reference electrode and a sensor electrode sensitive to a particular blood parameter such as pH or calcium, potassium or
chloride concentration. A bypass path for the electrical current interference is provided by a pair of noise-reduction electrodes lo-
cated on opposite sides of the reference and sensor electrodes and interconnected by an amplifier having a relatively low output
impedance and a relatively high input impedance. The electrical current interference bypasses the signal electrodes by flowing di-
rectly into the amplifier's output terminal, such that the reference and sensor electrodes develop a potential between them that is
independent of the electrical current interference.

FOR THE PURPOSES OF INFORMATION ONLY

Codes used to identify States party to Ihe PCT on Ihc front pages of pamphlets publishing international
applications under the PCX

AT

Austria

AU

Australia

Bft

Barbados

BE
BF

Belgium
Burkina Faso

BC

Bulgaria

Kl

Benin

BR

Brazil

CA

Canada

CF

Central African Republic

CO

Congo

CH

Switzerland

O

CSte iTIvoirc

CM

Cameroon

cs

Cwchostovakia

cz

CVcch Rcpobfic

OE

Germany

DK

Denmark

ES

Spain

Fl

Finland

FR
CA
GB
CN
CR
HU
IE
IT
JP
KP

Kit

KZ

U

US

LU

MC

rvtc

Ml.

MN

France

United Kingdom

Guinea

Greece

Hungary

Ireland

My

Democratic Peopled Republic
of Korea

Republic of Korea

Kazakhstan

IJecfiicmtcur

Srilanka

tjuxembourg

Madagascar
Mali

Mongolia

MR

Mauritania

MW

Malawi

NL

Netherlands

NO

Norway

HZ

New Zealand

PL

Poland

PT

Portugal

RO

Romania

RU

Russian Federation

SO

Sudan

SE

Sweden

SK

Slovak Republic

SN

su

Soviet Union

TD

Chad

TG

Togo

UA

Ukraine

US

United States of America

VH

Vict Nam

WO 93/09433

PCT/US92/09678

1

ELECTROCHEMICAL MEASUREMENT SYSTEM
HAVING INTERFERENCE REDUCTION CIRCUIT

BACKGROUND OF THE INVENTION

This invention relates generally to systems for
electrically measuring certain chemical characteristics of
fluids, e.g., concentration of certain analytes such as
ions, gases and metabolites in human blood, and, more
5 particularly, to electrical circuits for reducing the
effects of electrical interference in such measurement
systems .

Systems of this general kind can take the form
of blood chemistry diagnostic systems integrated into

10 infusion fluid delivery systems of the kind commonly used
in hospital patient care. Such fluid delivery systems
infuse nutrients, medications and the like directly into
the patient at a controlled rate and in precise quantities
for maximum effectiveness. Infusion fluid delivery

15 systems are connected to a patient at an intravenous (IV)
port, in which a hollow needle /catheter combination is
inserted into a blood vessel of the patient and thereafter
an infusion fluid is introduced into the vessel at a
controlled rate, typically using a peristaltic pump.

20 Blood chemistry monitoring systems that are combined with
infusion delivery systems of this kind use the IV port to
periodically withdraw a; blood sample, perform measurements
of blood ion concentrations and the like, and then discard
the blood or reinfuse it into the patient. The system

25 then resumes delivery of the infusion fluid.

Such combined infusion fluid delivery and blood
chemistry monitoring systems include an infusion line and
catheter through which the infusion fluid is provided to
the patient and blood samples are withdrawn. The infusion
30 line incorporates an electrode assembly having
electrochemical sensors that are periodically exposed to

WO 93/09433

PCT/US92/09678

the blood samples and thereby provide electrical signals
to an analyzer for conversion into corresponding blood
chemistry data. A control unit periodically halts
delivery of the infusion fluid for a brief interval ,
5 during which time a blood sample is withdrawn from the
patient into the infusion line and routed to the electrode
assembly, which then generates the electrical signals.
After the electrical signals have been received by the
analyzer, the control unit disposes of the blood or
10 reinfuses it into the patient, and the flow of infusion
fluid is resumed.

The electrode assembly typically includes a
reference electrode and a plurality of sensor electrodes
that are each sensitive to a particular ion of interest.

15 All of the electrodes are embedded in the base of the
electrode assembly. Electrochemical sensors generate
electrical signals, either a voltage or a current, only in
response to contact with the particular species to which
they are sensitive, and therefore provide selective

20 measurement of the amount of that species in the blood.
Sensor electrodes -can be provided to measure, for example,
partial pressure of oxygen (pO*) and carbon dioxide (pC0 2 ) ,
glucose, calcium, hydrogen ion, chloride, potassium, and
sodium*

25 The accuracy of the measurements described above

can be adversely affected by any electrical current
interference, usually originating at the patient, that is
conducted along the infusion tube by the blood and the
infusion fluid. Appropriate low-pass filtering of the

30 electrical potential measurements can reduce the effects
of this noise; however, substantial inaccuracies remain.
Movement of the infusion tube relative tb the patient
provides even greater noise and makes the task of
filtering or otherwise reducing the effects of the noise

35 even more difficult.

WO 93/09433

PCT/US92/09678

It should therefore be appreciated that there is
a need for an electrochemical measurement system of this
particular kind that is less susceptible to interference
from electrical current noise being conducted along the
5 fluid line. The present invention fulfills this need.

X SUMMARY OF THE INVENTION

This invention resides in an apparatus , and
related method, for measuring a predetermined parameter of
an electrically-conductive fluid located in a tube, which

10 are effective in substantially eliminating the adverse
effects of any electrical current interference being
conducted along the tube from a noise source at one end of
the tube. The apparatus and method are particularly
useful - as part of an infusion delivery system, in

15 analyzing of blood chemistry.

More particularly, the apparatus includes an
electrode assembly having a reference electrode and a
plurality of sensor electrodes located at spaced-apart
locations along a fluid path, along with signal amplifier

20 means for sensing the voltage between the reference
electrode and each sensor electrode and for providing a
corresponding voltage signal indicative of a predetermined
parameter of the contained fluid, for which the particular
sensor is sensitive* The sensor electrodes can include

25 ion-selective electrodes and other types of
electrochemical sensors. First and second noise-reduction
electrodes also are located in the electrode assembly, on
opposite sides of the reference and sensor electrodes. A
noise-reduction amplifier having an input terminal with a

30 high impedance and an output terminal with a low impedance
is connected between the first and second noise-reduction
electrodes, with its input terminal connected to the
electrode furthest from the noise source and with its

WO 93/09433

PCT/US92/09678

10

output terminal connected to the electrode closest to the
noise source. Electrical current interference thereby is
diverted through the noise-reduction amplifier, bypassing
the portion of the infusion tube where the reference and
sensor electrodes are located. The voltage signals
produced by the signal amplifier means thereby are
substantially unaffected by that electrical current
interference.

In other, more detailed features of the
invention, the noise-reduction amplifier takes the form of
an operational amplifier with its negative input terminal
connected to the noise-reduction electrode located
furthest from the noise source and with its. positive input
15 terminal connected to a ground reference. The electrical
current interference typically is only ac, and the noise-
reduction amplifier is operable to bypass th& entire
bandwidth of the ac current.

Other features and advantages of this invention
20 should become apparent from the following description of
% the preferred embodiment, taken in conjunction with the
accompanying drawings, which illustrate, by way of
example, the principles of the invention.

TVRTRP PESHRTPTION Q F-THK RKAWINGS

25 FIG. 1 is a schematic diagram of a combination

infusion fluid delivery and blood chemistry analysis
system in accordance with a preferred embodiment of the
invention, shown being coupled to the arm of a patient.

FIG. 2 is a schematic circuit diagram of an
30 electrode/amplifier assembly having a noise-reduction
circuit, the assembly being part of the analysis system of
FIG. 1.

WO 93/09433

PCT/US92/09678

5

FIG. 2A is a schematic circuit diagram of one
equivalent circuit for each electrode in the
electrode/amplifier assembly of FIG. 2.

FIG. 2B is a schematic circuit diagram of an
5 alternative equivalent circuit for each electrode in the
electrode/amplifier assembly of FIG. 2.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The following description of the preferred
embodiment of the invention is not to be taken in a
10 limiting sense, but is made merely for the purpose of
illustrating the general principles of the invention. The
description is of the best mode presently contemplated for
carrying out the invention.

With reference to FIG. 1, there is shown an
15 infusion fluid delivery and blood chemistry analysis
system in use connected to the arm 11 of a patient. An
infusion pump 13, under the control of a controller 15,
pumps an infusion fluid from a fluid source 17 to a blood
vessel in the patient's arm via an infusion tube 19 and
20 hollow needle 21. An electrode assembly 23 is located in
the middle of the infusion line and arranged such that the
infusion fluid passes through it on its way to the
patient.

_ Periodically, the controller 15 conditions the

25 pump 13 to interrupt its pumping of the infusion fluid to
the patient and, instead, to reverse direction and draw a
blood sample from the patient. This blood sample is drawn
rearwardly through the infusion tube 1? as far as the
electrode assembly 23, to allow the assembly to measure
30 certain characteristics of the blood. After the
measurements have been completed, the pump reinfuses the
blood sample back into the patient, and then resumes

WO 93/09433

PCTAJS92/09678

pumping the infusion fluid.

The electrode assembly 23 is depicted in greater
detail in FIG. 2. It includes a single reference
electrode 25 and four separate sensor electrodes 27a-27d
5 located at spaced location along the fluid flow path and
arranged to contact the fluid flowing through it- Each of
the sensor electrodes includes an electrochemical sensor
and it is adapted to develop between it and the reference
electrode a voltage potential that varies in accordance

10 with a predetermined parameter of the adjacent fluid to
which the electrochemical sensor is sensitive. Examples
of parameters that are commonly measured in this fashion
include pH, concentrations of sodium, potassium and
calcium, and glucose, hematocrit, and partial pressures of

15 oxygen (pO,) and carbon dioxide (pC0 2 ) . Amplifiers 29a-29d
are arranged to amplify the differential voltages provided
by the reference electrode and the respective sensor
electrodes 27a-27d, to provide amplified measurement
signals for output on lines 3la-31d.

20 m blood chemistry analysis systems like that

depicted in FIG. 1, it is known that electrical
interference in the form of an undesired electrical
current can originate at the patient, and be conducted
along the infusion tube 19 by the contained fluid, i.e.,

25 infusion fluid and/or blood, and thus can interfere with
the potential measurements being made. This electrical
current interference has only ac components and is
affected substantially by movement of the patient and/or
the infusion tube. The current affects the voltage

30 potential measurements in accordance with the inherent
resistivity of the fluid(s) located between the reference
electrode 25 and each sensor electrode 27a-27d.

In accordance with the invention, a bypass path
for the electrical current interference is provided by an

WO 93/09433 PCT/US92/09678

7

operational amplifier 33 connected between first and
second noise-reduction electrodes 35 and 37 f respectively,
situated on opposite sides of the reference electrode 25
and the plurality of sensor electrodes 27a-27d. One
5 suitable form for the electrode assembly is described in
detail in copending, commonly- assigned U.S. patent
application Serial No. 07/581,803, filed in the name of
David K. Wong and entitled "Electrochemical Sensor
Apparatus and Method , " which is incorporated by reference.

10 In particular, the operational amplifier's negative, or
inverting, input terminal is connected to the noise-
reduction electrode 35 located furthest from the patient,
while the amplifier's output terminal is connected to the
noise-reduction electrode 37 located closest to the

15 patient. The amplifier's positive, or non-inverting,
input terminal is connected to a ground reference.

As is conventional, the operational amplifier 33
has a relatively high input impedance that is many orders
of magnitude greater than its relatively low output

20 impedance. Consequently, noise currents originating at
the patient and flowing along the electrically-conductive
fluid in the infusion tube 19 to the electrode assembly 23
are readily diverted to the operational amplifier's output
terminal, which functions much like a current sink. The

25 current thereby is precluded from flowing along the fluid
located between each signal electrode 27a-27d and the
reference electrode 25. The voltage measurements made
between these electrodes thereby are substantially
unaffected by this electrical current interference

30 originating at the patient.

The noise-reduction electrodes 35 and 37 can be
of any suitable construction. Preferably, *£he first
noise-reduction electrode 35 takes the form of a bare
silver, silver-plated steel, or stainless steel pin in
35 direct contact with the infusion fluid. The second noise-

WO 93/09433

PCT/US92/09678

reduction electrode 37 may be of similar construction or
may take the form of an ion-sensitive electrode, e.g., a
sodium-sensitive electrode, like the sensor electrodes
27a-27d.

5 The reference electrode 25, the sensor

electrodes 27a-27d, and the noise-reduction electrodes 35
and 37 typically are considered to have an equivalent
electrical circuit in the form of a resistor 39 in series
with a battery 41 of specified voltage. This is depicted
10 in FIG. 2A.

The electrodes alternatively can be considered
to have more complex equivalent circuits such as a
parallel combination of a resistor 43 and capacitor 45 in
series with a battery 47, as depicted in FIG. 2B.

15 in the ease of the reference electrode and

sensor electrodes 27a-27d, the batteries in the equivalent
circuits yield dc voltage differences that are amplified
by the amplifiers 29a-29d. The electrical current flowing
through the electrodes is negligible, so the electrode

20 resistance is of minimal significance. Further, the dc
voltage differences provided by the noise-reduction
electrodes 35 and 37 are of no concern, because the noise-
reduction circuit functions merely as a bypass path for ac
electrical current interference originating at the

25 patient. A feedback capacitor 49 for the operational
amplifier 33 limits the circuit's ac bandwidth to an
appropriate range, to overcome the bandwidth of the noise
signal.

It should be appreciated from the foregoing
30 description that the present invention provides an
improved system for electrically measuring certain
chemical Characteristics of electrically-conductive fluids
such as blood located within a tube and subject to

WO 93/09433 PCT/US92/09678

9

electrical current interference. The measurements are
made by measuring the voltage potential between a
reference electrode and a sensor electrode located in the
fluid line. A bypass path for the electrical current
5 interference is provided by a pair of noise-reduction
electrodes that are located on opposite sides of the
reference and sensor electrodes and interconnected by an
amplifier having a relatively low output impedance and a
relatively high input impedance. In particular, the

ID electrical current interference flows directly into the
amplifier's output terminal, thereby ensuring that the
reference and sensor electrodes develop a potential
between them that is independent of the interference .
Noise reductions on the order of 120db are readily

15 achievable.

Although the invention has been described in
detail with reference to the presently preferred
embodiment, those of ordinary skill in the art will
appreciate that various modifications can be made without
20 departing from the invention. Accordingly, the invention
is defined only by the following claims.

WO 93/09433

PCT/US92/09678

10

Claims

1. Apparatus for measuring a predetermined
parameter of an electrically-conductive fluid located in
a tube and used in an environment where an undesired
electrical current can be conducted by the fluid from a
noise source at one end of the tube, the apparatus
comprising:

a reference electrode and a sensor
electrode adapted to be attached to a tube at spaced-apart
locations, contacting an electrically-conductive fluid in
the tube;

signal amplifier means for amplifying the
voltage between the reference, electrode and the sensor
electrode and for providing a corresponding amplified
signal;

first and second noise-reduction electrodes
adapted to be attached to the tube at spaced-apart
locations, contacting the electrically conductive fluid in
the tube, such that the reference and sensor electrodes
are located between the first and second noise-reduction

electrodes; and

noise-reduction amplifier means having an

input terminal with a high impedance and an output
terminal with a low impedance, the noise-reduction
amplifier means being connected between the first and
second noise-reduction electrodes, with its input terminal
connected to the noise-reduction electrode furthest from
the noise source and with its output terminal connected to
the noise-reduction electrode closest to the noise source,
such that any electrical current originating at the noise
source bypasses the portion of the electrically-conductive
fluid located in the tube between the reference and sensor
electrodes by flowing instead through the noise-reduction
amplifier means, whereby the amplified signal produced by
the signal amplifier means is substantially unaffected by
that electrical current.

WO 93/09433

PCT/US92/09678

11

2. Apparatus as defined in claim 1, wherein
the noise-reduction amplifier means includes an
operational amplifier having a negative input terminal
connected to the noise-reduction electrode that is

5 furthest from the noise source, a positive input terminal
connected to a ground reference , and an output terminal
connected to the noise-reduction electrode that is closest
to the noise source,

3. Apparatus as defined in claim 1, wherein:
the apparatus further includes one or more

additional sensor electrodes; and

the signal amplifier means include a
5 . plurality of amplifiers, each amplifier for .amplifying the
voltage between the reference electrode and a separate
sensor electrode and for providing a corresponding
amplified signal.

4. Apparatus as defined in claim 1, wherein:
the noise source generates an ac electrical

current having a bandwidth; and

the noise^reduction amplifier means is
5 adapted to conduct the ac electrical current over the
current's entire bandwidth.

5. Apparatus es defined in claim 1, wherein:
the tube is connected at one end to a

patient;

the electrically-conductive fluid is blood;

5 and

the reference electrode and the sensor
electrode are adapted to develop between them a voltage
that is indicative of a predetermined parameter of the
blood.

6. Apparatus as defined in claim 1, wherein
the first and second noise-reduction electrodes are pins

WO 93/09433

PCT/US92/09678

12

formed of silver, silver-plated steel, or stainless steel.

7. Apparatus as defined in claim l f wherein:
the noise-reduction electrode located

furthest from the noise source is a pin formed of silver,
silver-plated steel, or stainless steel; and

the noise-reduction electrode located
closest to the noise source is sensitive to a
predetermined parameter of the electrically-conductive
fluid.

8. Apparatus for measuring a predetermined
parameter of blood drawn from a patient into an
intravenous tube, the apparatus comprising;

a reference electrode and a sensor
electrode adapted to be attached at spaced-apart locations
in an intravenous tube into which blood can be drawn from
a patient to contact the two electrodes, wherein a
potential develops between the two electrodes that is
indicative of a predetermined parameter of the blood;

wherein electrical current interference
originating at the patient can be conducted along the
intravenous tube by blood contained in the tube;

f irst and second noise-reduction electrodes
adapted to be attached at spaced-apart locations in the
intravenous tube, in contact with blood drawn into the
tube, such that the reference and sensor electrodes are
located between the first and second noise-reduction
electrodes; and

noise-reduction amplifier means having an
20 input terminal with high impedance and an output terminal
with a low impedance, the noise-reduction amplifier means
being connected between the first and second noise-
reduction electrodes, with the input terminal connected to
the noise-reduction electrode furthest from the patient
and with the output terminal connected to the noise-
reduction electrode closest to the patient, such that any

10

15

25

WO 93/09433

PCT/US92/09678

13

electrical current originating at the patient bypasses the
portion of the tube between the reference and sensor
electrodes by flowing instead through the noise-reduction
30 amplifier means, whereby the potential developed between
the reference and sensor electrodes is substantially
unaffected by that electrical current.

9. Apparatus as defined in claim 8, wherein
the noise-reduction amplifier means includes an
operational amplifier having a negative input terminal
connected to the noise-reduction electrode that is

5 furthest from the patient , a positive input terminal
connected to a ground reference , and an output terminal
connected to the noise-reduction electrode that is closest
to the patient.

10. Apparatus as defined in claim 8, wherein:
the electrical current noise originating at

the patient is an ac current having a. bandwidth; and

the noise-reduction amplifier means is
5 adapted to conduct the ac current over the current's
entire bandwidth.

11. Apparatus, as defined in claim 8, wherein
the first and second noise-reduction electrodes are pins
formed of silver; silver-plated steel, or stainless steel.

12. Apparatus as defined in claim 8, wherein:
the noise-reduction electrode located

furthest from the noise source is a pin formed of silver,
silver-plated steel, or stainless steel; and

the noise-reduction electrode located
5 closest to the noise source is sensitive to a
predetermined parameter of the electrically-conductive
fluid.

WO 93/09433

PCT/US92/09678

10

14

13 . A method for measuring a predetermined
parameter of blood drawn from a patient into an
intravenous tube, the method comprising steps of;

providing an electrode and infusion tube
assembly having a reference electrode and a sensor
electrode located at spaced apart locations, the sensor
electrode being sensitive to a particular parameter of
blood;

arranging the electrode and infusion tube
assembly such that blood can be drawn from a patient into
contact with one or both of the reference and sensor
electrodes/wherein a potential develops between the two
electrodes that is indicative of the predetermined
parameter of the blood, and wherein electrical current
interference originating at the patient can be conducted
along the infusion tube by the blood contained in the
tube; and

connecting a noise-reduction amplifier
between two noise-reduction electrodes located on opposite
sides of the reference and sensor electrodes, wherein the
amplifier has a high-impedance input terminal connected to
the noise reduction electrode located furthest from the
patient and a low-impedance output terminal connected to
the noise reduction electrode closest to the patient, such
that any electrical current interference originating at
the patient bypasses the reference and sensor electrodes
by flowing instead through the noise-reduction amplifier,
whereby the potential developed between the reference and
sensor electrodes is substantially unaffected by that
30 electrical current.

15

20

25

WO 93/09433

PCT/US92/09678

V

FIG. 2

JZ3.

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Z 7e^Z7j

1

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<43

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FIG. 2B

SUBSTITUTE SHEET

INTERNATIONAL SEARCH REPORT

lirtcrnauooal Application No

PCT/US 92/09678

[ 1. CLASSIFICATION OF SUBJECT MATTER (if several classification symbols apply, indicate all)»
According to International Patent Classification (IPO or to both National Classification and IPC

lint, CI. 5 G01N33/49; G01N27/26

IL FIELDS SEARCHED

Minimum Documentation Searched 7

Classification System

Classification Symbols

Int. CI. 5

G01N

Documentation Searched other than
to the Extent that such Documents are

Included in the Fields Searched 9

j m.

DOCUMENTS CONSIDERED TO BE RELEVANT*

Citation of Document, " with indicatioD, where appropriate, of the relevant passages"

US,A,4 573 968 (PARKER)
4 March 1986 ^
see column 2, line 3 - column 5, line 25;
figures 1-3

W0,A,8 902 593 (HARMAN)

23 March 1989 .

see page 9, line 12 - page 18, line 8;

figures 1-7

US,A,4 818 361 (BURGESS)

4 April 1989

see abstract; figures

1,8,13

1,8,13

1>8,13

° Special categories of ciud docomrnts : 10

-A* document defining the general state of the art which is not

considered to be of owScular relevant*
'ET earlier document but published on or after the international

filing date

*L* document which may throw doubts on priority daimts) or
which b dted to establish the piiblkathw date of another
citation or other special reason (as specified)

*0* document referring to an oral dhdosure, use. exhibition or

document published after the international filing date
or priority date and not in conflict with the api^a?™**"
■ iw u W«r*nd the orinciolc or theory muferiywg the

*T* later

died »" understand the principle or theory

t published prior to the international filing date but

later than the priority date daimed

•X* document of particular relevance; the ^^J^^ 0
cannot be considered novel or cannot be considered to
involve an inventive step

*Y* document of particular relevance; the cWmed invents
cannot be considered to involve an toveonve stepwb«the

in the art.

•4' document member of the same patent family

IV, CERTIFICATION

I Date of the Actual Completion of the International Search

03 MARCH 1993

Dm of Milling of this Inttnnliooil Stare* Report

J LIE S3

| International Searditag Authority

EUROPEAN PATENT OrTICE

Signature of Authorized Officer

R.A.P. BOSMA

Tim PCT/BA/nO tmtmt HmttOmmr W

ANNEX TO THE INTERNATIONAL SEARCH REPORT 920 9678
ON INTERNATIONAL PATENT APPLICATION NO. g 57244

Patent document
cited in search resort

Publication
date

Patent family
mcinbcrfs)

Publication
date

US-A-4573968

04-03-86

None

W0-A-8902593

23-03-89

EP-A-
JP-T-

0331696
2501162

13-09-89
19-04-90

US-A-4818361

04-04-89

None

i

I For more detmifcaboot this annex: see Official Journal of the European Patent Office, No. 12/82

THIS PA6E BUNKiuspto)